Studies using cultured hippocampal neurons from fetal mouse trisomy 16 (Ts16), a model for Down syndrome showed that there is a significant decrease in the rate of depolarization of the action potential, and in the voltage-dependent sodium current for trisomy 16 compared to control hippocampal neurons. High voltage-activated calcium currents however were significantly larger in trisomy neurons compared to control. Withdrawing nerve growth factor (NGF) from the culture medium of control dorsal root ganglion (DRG) neurons resulted in a smaller potassium current compared to those maintained in NGF-containing medium. Trisomy 16 DRG neurons grown in medium that had NGF withdrawn however displayed a larger potassium current. The depolarization rate and sodium current was unaffected in either control or trisomy neurons. Control and trisomy 21 DRG neurons grown in the absence of NGF displayed prolonged action potentials with a slower rate of depolarization. Trisomy 16 DRG neurons in culture had a 2-fold greater incorporation of [1-14C]arachidonate than control neurons, primarily into a lipid resembling phosphatidic acid.